Methods and Compositions Related to Clot Binding Compounds

Abstract

Disclosed are compositions and methods related to clot binding compounds. The disclosed targeting is useful for treatment of cancer and other diseases and disorders.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of U.S. Provisional Application No. 60 / 883,229, filed Jan. 3, 2007, and to U.S. Provisional Application No. 60 / 883,890, filed Jan. 8, 2007, both herein incorporated by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH[0002]This invention was made with government support under CA119335 awarded by the National Cancer Institute. The government has certain rights in this invention.FIELD OF THE INVENTION[0003]The present invention relates generally to the fields of molecular medicine and cancer biology and, more specifically, to clot binding compounds that selectively home to tumor vasculature.BACKGROUND OF THE INVENTION[0004]A major hurdle to advances in treating cancer is the relative lack of agents that can selectively target the cancer while sparing normal tissue. For example, radiation therapy and surgery, which generally are localized treatments, can cause substantial damage to n...

AI Technical Summary

Benefits of technology

[0018]In one example, the conjugate can have a therapeutic effect. This can be achieved by the enhanced clot formation that occurs because of the conjugate. This effect can be enhanced by the delivery of a therapeutic agent to the site of the tumor or wound site.

Problems solved by technology

A major hurdle to advances in treating cancer is the relative lack of agents that can selectively target the cancer while sparing normal tissue.

For example, radiation therapy and surgery, which generally are localized treatments, can cause substantial damage to normal tissue in the treatment field, resulting in scarring and loss of normal tissue.

Chemotherapy, in comparison, which generally is administered systemically, can cause substantial damage to organs such as the bone marrow, mucosae, skin and small intestine, which undergo rapid cell turnover and continuous cell division.

As a result, undesirable side effects such as nausea, loss of hair and drop in blood cell count often occur when a cancer patient is treated intravenously with a chemotherapeutic drug.

Such undesirable side effects can limit the amount of a drug that can be safely administered, thereby hampering survival rate and impacting the quality of patient life.

The first generation of nanoparticles used in tumor treatments rely on “leakiness” of tumor vessels for preferential accumulation in tumors; however, this enhanced permeability and retention (EPR) is not a constant feature of tumor vessels (Sinek 2004) and even when present, still leaves the nanoparticles to negotiate the high interstitial fluid pressure in tumors (Sinek 2004; Boucher 1990).

Specific targeting of nanoparticles to tumors has been accomplished in various experimental systems (DeNardo 2005; Akerman 2002; Cai 2006), but the efficiency of delivery is generally low.

Images